Naval and customs officers seized 4.4 tonnes of cocaine which had been hidden in four soy flour containers destined for Lome, Togo, in Montevideo port and another 1.5 tonnes on a ranch, local reports said.
Uruguay’s navy has said the bust is the “biggest blow to drug trafficking in the country’s history”, beating a previous record haul earlier this year.
In November, authorities uncovered a container with 3 tonnes of cocaine which would have been sent to Benin.
Jaime Borgiani, Uruguay’s customs director, said the 4.4 tonnes found in Montevideo would have had an estimated value of $1bn in the European market.
Drug traffickers have used Uruguay as a transit point to move cocaine from Latin America to Africa and Europe as worldwide demand for the drug has increased.
Mr Borgiani’s predecessor, Enrique Canon, resigned in August after 4.5 tonnes of cocaine was discovered in Hamburg, Germany, on a container ship which had travelled from Uruguay.
This week’s bust in Montevideo came together when scanners at the port found “anomalies” in the containers, according to officials.
Authorities were apparently suspicious because the export firm in question was not known for transporting large quantities of soya, which is not widely consumed in Africa.
Diego Perona, a spokesperson for the navy, said more than 3,000 bricks of cocaine, each weighing 1.1kg, were found before they were due to be loaded onto an Italian-registered ship, according to local media reports.
Mr Borgiani said it is not known exactly where the cocaine came from but it had been loaded onto trucks at a ranch in the south-western Soriano region, 180 miles from Montevideo, on Tuesday.
Police raided the ranch, where they arrested its owner and his son, and seized a further 1.5 tonnes of the drug, according to Uruguay’s El Pais newspaper.
“The important thing is to show the world and drug traffickers that you don't mess around with Uruguayan customs,” Mr Borgiani told AFP.
“We've taken the necessary steps to rid the country of this scourge.”
The bust in Uruguay is one of a number of major drug seizures this year.
In the UK, authorities seized nearly 1.3 tonnes of heroin with a street value of £120m in September, in what was called “one of the largest [seizures] ever in Europe”.